We will employe isolated intrapulmonary arteries, veins and airways dissected from lung lobes of rabbit, cat, dog, subhuman primate and man to determine more fully their roles in pulmonary function and disease. Objectives are (1) to describe more fully the morphology and ultrastructure; (2) to compare functional characteristics of contractile activity; (3) to determine reactivity to circulating and locally-released agonists and to therapeutic agents useful in certain pulmonary diseases; (4) to assess the effects of ions on this reactivity; (5) to test the effects of hypoxia, hypercapnia and acidosis; and (6) to study the anaphylactic response. Isometric and isotonic contraction and relaxation, tissue ion and adenosine 3'5' monophosphate (cAMP) levels and radiocalcium uptake, efflux and tissue distribution are some of the parameters to be measured. Objective No. 1 will be met by a) light microscopy of smooth muscle orientation, extracellular space and elastic and connective tissue component and b) electron microscopy to examine cell organelles (sarcoplasmic reticulum, mitochondria, myofilaments, etc.). Satisfying objective 2 will involve tension-tension and length-tension studies, measurement of maximum tension output, etc. Agents to be tested for No. 3 include: norepinephrine, epinephrine, acetylcholine, histamine, serotonin, angiotensin, bradykinin and prostaglandins; antiasthmatics and drugs for obstructive airway disease, pulmonary hypertension and edema (isoproterenol, theophylline, diazoxide, morphine, cromolyn sodium, etc.). Dose-response relationships will be determined in the absence and presence of specific antagonists. No. 5 will be met by studying effects of test substances on tissue Ca2, K, Na ions and Cl ion content and the role of tissue Ca2 ion pools in contraction; No. 5 by repeating many of the above experiments under conditions of altered pH, O2 and CO2 levels; No. 6 by comparing antigen- induced contractile responses of tissues from sensitized animals with those elicited by possible mediators in the presence and absence of specific antagonists and agents acting on mast cells.